CLINICAL STUDY Parallel downregulation of retinol-binding protein-4 and adiponectin expression in subcutaneous adipose tissue of non-morbidly obese subjects Montserrat Broch 1,2 , Maria Teresa Auguet 1,2,3 , Rafael Ramı ´rez 3 , Montserrat Olona 4 , Carmen Aguilar 1,2 , Ana Megia 2,5,9 , Maria Jose ´ Alcaide 6 , Rosa Pastor 7 , Salome ´ Martı ´nez 8 , Enric Caubet 10 , Antonio Garcia-Espan ˜a 11 and Cristo ´bal Richart 1,2,3 1 CIBER (CB06/03) Fisiopatologia de la Obesidad y Nutricio ´n, Instituto de Salud Carlos III, Avda Monforte de Lemos, Madrid, Spain, 2 Department of Medicine and Surgery, Universitat Rovira i Virgili. Sant Llorenc ¸ 21, 43201 Reus, Tarragona, Spain, 3 Internal Medicine Service, 4 Epidemiology and Statistic Unit, 5 Diabetes and Endocrinology Service, 6 Surgery Service, 7 Hormonal Laboratory and 8 Pathology Service, Hospital Universitari de Tarragona Joan XXIII, Dr Mallafre ´ Guasch s/n 43007, Tarragona, Spain, 9 CIBER (CB07/08) Diabetes, Instituto de Salud Carlos III, Avda Monforte de Lemos, Madrid, Spain, 10 Surgery Service, Hospital de Sant Pau i Santa Tecla, Rambla Vella, 14, 43003, Tarragona, Spain and 11 Institut d’Investigacio ´ Sanitaria Pere Virgili, Sant Llorenc ¸ 21, 43201 Reus, Tarragona, Spain (Correspondence should be addressed to M Broch; Email: mbroch.hj23.ics@gencat.cat) Abstract Context and objective: Adipokines are involved in the etiopathology of obesity-related disorders. Since the role of adipokine retinol-binding protein-4 (RBP4) in obesity remains uncertain and its relationship with other adipokines and inflammatory markers has not been examined in detail, we investigated the relationships of RBP4 mRNA expression and circulating protein levels with obesity, anthropometric and metabolic variables, as well as with obesity-related inflammatory markers adiponectin and C-reactive protein. Subjects and methods: One-hundred and twenty-five subjects participated, 36 lean (body mass index (BMI): !25 kg/m 2 ) and 89 obese (overweight/obese; BMI: R25!40) whose anthropometric and metabolic variables were assessed. mRNA expression was quantified by real-time PCR in subcutaneous adipose tissue (s.c.-AT) of 46 subjects. Results: There was a tendency for circulating RBP4 levels to positively correlate with waist circumference (bZ0.29, PZ0.08; R 2 Z0.08), but there was no significant association with the obesity-related parameters analysed. RBP4 and adiponectin mRNA expression levels were similarly downregulated in the s.c.-AT of obese subjects (0.5-fold); however, RBP4 downregulation did not affect its circulating protein levels. The expression of RBP4 and adiponectin was positively correlated even after controlling for confounding factors (bZ0.59, P!0.0001; R 2 Z0.40). Conclusions: In our population, RBP4 circulating levels were not significantly correlated with obesity- related parameters, although a tendency to correlate with waist circumference suggests a relationship with insulin resistance and other metabolic disorders. In addition, our results suggest that the production of RBP4 byother tissues such as liver, rather than s.c.-AT, may be involved in regulating RBP4 circulating levels. European Journal of Endocrinology 161 87–94 Introduction In addition to its main metabolic role of storing energy in the form of fat, adipose tissue (AT) is now considered an active endocrine organ that secretes a variety of bioactive peptides. These peptides are known as ‘adipokines’ and they coordinate biological processes such as energy metabolism, immune and neuro- endocrine functions (1–3). Obesity is a condition that is associated with low-level chronic inflammation, insulin resistance (IR), hyper- lipidaemia and other metabolic disorders (4). There is now growing evidence that adipokines are important in the etiopathology of obesity-related disorders, either through a traditional (circulating) hormonal effect or by a local action in the AT (5). Since the circulating levels of a recently identified adipokine that acts as a carrier of retinol (vitamin A) in the blood, retinol-binding protein-4 (RBP4), have been positively correlated with obesity and IR in an adipocyte-specific glucose transporter 4 knock-out mouse (Glut4 K/K ) model (6), and, in this model, an insulin-sensitising drug reduced the elevated levels of RBP4 transcripts in AT as well as its systemic levels (6), it has been proposed that RBP4 may be behind the adipocyte–muscle connection that links obesity and IR European Journal of Endocrinology (2009) 161 87–94 ISSN 0804-4643 q 2009 European Society of Endocrinology DOI: 10.1530/EJE-08-0866 Online version via www.eje-online.org Downloaded from Bioscientifica.com at 05/25/2020 07:41:22PM via free access